Univ Sao Paulo, Inst Phys, BR-05508090 Sao Paulo - Brazil
Total Affiliations: 5
Archives of Biochemistry and Biophysics;
JAN 1 2015.
Web of Science Citations:
The p23 protein is a chaperone widely involved in protein homeostasis, well known as an Hsp90 cochaperone since it also controls the Hsp90 chaperone cycle. Human p23 includes a 13-sheet domain, responsible for interacting with Hsp90; and a charged C-terminal region whose function is not clear, but seems to be natively unfolded. p23 can undergo caspase-dependent proteolytic cleavage to form p19 (p231-142), which is involved in apoptosis, while p23 has anti-apoptotic activity. To better elucidate the function of the human p23 C-terminal region, we studied comparatively the full-length human p23 and three C-terminal truncation mutants: p231\_117; p231-131 and p231\_142. Our data indicate that p23 and p19 have distinct characteristics, whereas the other two truncations behave similarly, with some differences to p23 and p19. We found that part of the C-terminal region can fold in an a-helix conformation and slightly contributes to p23 thermal-stability, suggesting that the C-terminal interacts with the 13-sheet domain. As a whole, our results suggest that the C-terminal region of p23 is critical for its structure-function relationship. A mechanism where the human p23 C-terminal region behaves as an activation/inhibition module for different p23 activities is proposed. (C) 2014 Elsevier Inc. All rights reserved. (AU)